Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations

Dvir Gatt, Inbal Golan Tripto, Eran Levanon, Noga Arwas, Guy Hazan, Soliman Alkrinawi, Aviv D. Goldbart, Micha Aviram

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations

    Abstract

    Background The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations. Methods Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed. Results Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones. Conclusions In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

    Original languageEnglish
    Pages (from-to)428-431
    Number of pages4
    JournalArchives of Disease in Childhood
    Volume109
    Issue number5
    DOIs
    StatePublished - 1 May 2024

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health

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